Perfusion Augmentation Through Exercise

Not Applicable

Not yet recruiting

• Conditions: Stroke, Ischemic
• Interventions: Behavioral: Aerobic treadmill training; Behavioral: Stretching exercise

• Registration Number: NCT05584605
• Lead Sponsor: University of Zurich

Brief Summary

Large cerebral vessel occlusion is a common phenomenon in the general population and accounts for 13-35% of ischemic strokes. Chronic stenosis in the large cerebral arteries is associated with cerebral hypoperfusion, cognitive decline and an increased risk of stroke or recurrent stroke, respectively.

Even with upgrowth of surgical or endovascular interventions, mechanical reopening of the occluded vessels is often not possible. Alternative treatment opportunities include minimal-to-moderate blood pressure elevation (typically by ceasing antihypertensives) waiting for collateral circulation to develop spontaneously. Another conservative approach to increase cerebral perfusion is aerobic exercising. Physical activity has shown to lead to cerebral blood flow increase, especially in activated brain areas of healthy human and rat models. However, it is remains unknown, how physiological adaptation to physical activity expresses in persons after stroke due to large vessel occlusion. Herein, it is hypothesized that aerobic exercise facilitates the development of an extensive and functional vascular collateral network in persons with ischemic stroke and perfusion compromise.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-15
• Status Verified: 2022-10
• Study First Submitted QC: 2022-10-13
• Last Update Submitted: 2022-10-13
• Study First Posted: 2022-10-18
• Last Update Posted: 2022-10-18
• Study Start: 2022-11
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Male and Female patients of 18 years of age or above
• Subjects after ischemic cerebral stroke (≥ 3 months) due to large vessel occlusion
• Subjects do not qualify for flow augmentation through ECIC bypass or endovascular treatment
• Persistent deficit in BOLD-CVR
• Functional Ambulatory Categories >2
• Discharged from hospitalization / inpatient rehabilitation
• Living independent before stroke (mRS ≤3)
• Written Informed Consent

Exclusion Criteria

• Severe cardiac disease, such as instable angina pectoris, pericarditis, heart failure (New York Health Association > II°), or hemodynamically significant valvular dysfunction
• Complete arterial stenosis
• Peripheral artery disease with mild to moderate claudication at < 200m or 200-1000m of walking
• Contra-indication, such as a history of a seizure, prior electroconvulsive therapy, deep brain stimulators or other metal in the head, skull defect, pacemaker, neuroleptic medication
• Inability to follow the procedures of the study, e.g., due to language problems (unable to follow to stage commands), psychological disorders (major depression), and / or a neurodegenerative disease (dementia)
• Known or suspected non-compliance, documented drug, or alcohol abuse
• Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
aerobic treadmill training	Aerobic treadmill training	Progressive graded, high-intensity aerobic treadmill training is delivered over 36 sessions at a frequency of 3x per week for 30-50 minutes of training per session over a period of 3 months. If possible, the training intensity is progressed from 40% to 80% of heart rate reserve, according to the supervising therapist.
stretching exercise	Stretching exercise	The control intervention includes stretching exercise therapy similarly heart rate controlled within limits up to 20% of heart rate reserve over 36 sessions at a frequency of 3x per week for 30 minutes.

Primary Outcome Measures

Name	Time	Method
Brain imaging - cerebrovascular reactivity (CVR) by BOLD-fMRI	post-intervention (12 weeks)	Functional brain tissue perfusion and tissue at risk based on cerebrovascular reactivity by blood oxygenation-level dependent functional magnetic resonance imaging (BOLD-fMRI), measured as the percentage BOLD signal change /mmHg CO2.

Secondary Outcome Measures

Name	Time	Method
Brain imaging - NOVA-qMRI	post-intervention (12 weeks)	Blood flow velocity based on non-invasive optimal vessel analysis quantitative magnetic resonance imaging
Brain imaging - Lesion volume	post-intervention (12 weeks)	based on 3D T1 weighted imaging, 3D Fluid-Attenuated Inversion Recovery (FLAIR), Diffusion-Eighted Imaging (DWI)
Six-Minute Walk Test (6MWT)	post-intervention (12 weeks) + follow-up (+3 months)	Functional walking capacity in meters
Motricity Index of the Lower Extremity (MI-LE)	post-intervention (12 weeks) + follow-up (+3 months)	Muscle strength assessment of three major muscle groups of the lower extremity with a total score ranging from 0 to 100 and higher scores indicating better performance.
5-Chair-Rise-Test	post-intervention (12 weeks) + follow-up (+3 months)	Functional muscle strength, measured in seconds to complete the task.
Brain imaging - intravoxel incoherent motion (IVIM)	post-intervention (12 weeks)	Functionality of brain microvasculature by measuring diffusion and perfusion components of tissue based on intravoxel incoherent motion
Ten-Meter Walk Test (10MWT)	post-intervention (12 weeks) + follow-up (+3 months)	Walking speed in m/s
Fugl-Meyer Assessment of the Lower Extremity (FMMA-LE)	post-intervention (12 weeks) + follow-up (+3 months)	Stroke-specific motor impairment index to assess lower limb motor function with a total score ranging from 0 to 34 and higher scores indicating better performance.
Montreal Cognitive Assessment (MoCA)	post-intervention (12 weeks) + follow-up (+3 months)	Screening assessment of cognitive functions with a maximum score of 30 points.
Stroop test	post-intervention (12 weeks) + follow-up (+3 months)	Assessment of executive function and inhibition
International Physical Activity Questionnaire (IPAQ)	post-intervention (12 weeks) + follow-up (+3 months)	self-reported physical activity
Word list learning	post-intervention (12 weeks) + follow-up (+3 months)	Assessment of memory function
Exercise stress testing	post-intervention (12 weeks)	Cycle ergometer testing with spirometry
Brain imaging - Collateral status	post-intervention (12 weeks)	Collateral status based on 3D time of flight angiography (TOF)
Digit Span Test / Corsi block	post-intervention (12 weeks) + follow-up (+3 months)	Assessment verbal and nonverbal working memory
European Quality of Life 5 Dimensions 5 Level (5Q-5D-5L)	post-intervention (12 weeks) + follow-up (+3 months)	Quality of life questionnaire that assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) on a 5-level scale ranging from 1 - no, 2 - slight, 3 - moderate, 4 - severe to 5 - extreme problems or unstable to.

Trial Locations

Locations (3)

Ambulante Reha Triemli Zürich; 🇨🇭 Zürich, Switzerland

Klinik Lengg AG; 🇨🇭 Zürich, Switzerland

University Hospital Zurich; 🇨🇭 Zürich, Switzerland